In this Phase III study 2,300 hospitalized adult patients (23 at this site) demonstrating severe sepsis will be randomized on a 1:1 ratio. They will receive either antithrombin III; 6,000 IU (bolus infusion over 30 minutes) followed by continuous infusion of 250 IU/h (3000 IU/12h) or placebo; equivalent volume of 1% albumin in water administered IV for 4 consecutive days. Patients will be evaluated for clinical responses to treatment on days 1-5 and 7 along with primary and secondary endpoints day 28 and days 56 and 90, respectively. The primary objectives are to demonstrate the safety of antithrombin III vs. placebo in the treatment of patients with severe sepsis, day 1-5 and 7 thru day 28 and to demonstrate the reduction of 28-day mortality of antithrombin III vs. placebo in the treatment of patients with severe sepsis. The secondary objectives are to demonstrate the safety of antithrombin III vs. placebo in the treatment of patients with severe sepsis, day 28-90, and to assess the survival time, the time from enrollment until discharge from the ICU and the organ function of the patient on days 28, 56, and 90. The GCRC will provide scatter nursing support for the pharmacokinetic blood samples and the core lab will prepare and ship the samples.